The leukotrienes and their biological activities, especially their role in various disease states, have been extensively studied. Their properties are described in the book Leukotrienes and Lipoxygenases, Ed., J. Rokach, Elsevier, N.Y., 1989.
Inhibitors of the 5-lipoxygenase enzyme will prevent the biosynthesis of the various leukotrienes, and hence have a beneficial effect in those disease states in which the leukotrienes contribute to the disease.
Various derivatives of hydroxylamine have been described as inhibitors of the 5-lipoxygenase enzyme. Representative compounds are to be found in the following patent documents: EP 196,184, EP 279,263, WP 87/04152 and U.K. 2,191,194. None of the above-mentioned compounds contains an indene nucleus, a distinguishing feature of the present invention. U.S. Pat. Nos. 3,647,858 and 3,654,349 describe certain indene derivatives, which differ considerably from the present invention in that they are carboxylic acids rather than hydroxamic acid derivatives. Hydroxamic acids are distinguished from carboxylic acids by being about 4 pK.sub.A units weaker as acids. The pK.sub.A values of hydroxamic acids (8-9) are such that they are largely un-ionized at physiological pH, whereas carboxylic acids (pK.sub.A 4-5) are fully ionized. Other physical-chemical properties, such as chelation ability, are also notably different between the two classes of functional groups.